Three dimensional fibrotic extracellular matrix directs microenvironment fiber remodeling by fibroblasts

Nizamoglu, Mehmet; Alleblas, Frederique; Koster, Taco; Borghuis, Theo; Vonk, Judith M.; Thomas, Matthew J.; White, Eric S.; Watson, Carolin K.; Timens, Wim; El Kasmi, Karim C.; Melgert, Barbro N.; Heijink, Irene H.; Burgess, Janette K.

doi:10.1016/j.actbio.2024.02.008

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Acta Biomaterialia

2024

DOI: 10.1016/j.actbio.2024.02.008

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Three dimensional fibrotic extracellular matrix directs microenvironment fiber remodeling by fibroblasts

Mehmet Nizamoglu,

Frederique Alleblas,

Taco Koster

et al.

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2024

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Pulmonary matrix-derived hydrogels from patients with idiopathic pulmonary fibrosis induce a proinflammatory state in lung fibroblasts in vitro

Fernandez Davila,

Singh,

Moore

et al. 2024

MBoC

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Idiopathic pulmonary fibrosis (IPF), one of the most common forms of interstitial lung disease, is a poorly understood, chronic, and often fatal fibroproliferative condition with only two FDA-approved medications. Understanding the pathobiology of the fibroblast in IPF is critical to evaluating and discovering novel therapeutics. Using a decellularized lung matrix derived from IPF patients, we generate three-dimensional (3D) hydrogels as in vitro models of lung physiology and characterize the phenotype of fibroblasts seeded into the hydrogels. When cultured in IPF ECM hydrogels, IPF fibroblasts display differential contractility compared to their normal counterparts, lose the classical myofibroblast marker α-smooth muscle actin, and increase expression of proinflammatory cytokines compared to fibroblasts seeded two-dimensionally (2D) on tissue culture dishes. We validate this proinflammatory state in fibroblast-conditioned media studies with monocytes and monocyte-derived macrophages. These findings add to a growing understanding of the lung microenvironment effect on fibroblast phenotypes, shed light on the potential role of fibroblasts as immune signaling hubs during lung fibrosis, and suggest intervention in fibroblast-immune cell crosstalk as a possible novel therapeutic avenue.

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Pulmonary matrix-derived hydrogels from patients with idiopathic pulmonary fibrosis induce a proinflammatory state in lung fibroblasts in vitro

Fernandez Davila,

Singh,

Moore

et al. 2024

MBoC

View full text Add to dashboard Cite

show abstract

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Three dimensional fibrotic extracellular matrix directs microenvironment fiber remodeling by fibroblasts

Cited by 1 publication

References 54 publications

Pulmonary matrix-derived hydrogels from patients with idiopathic pulmonary fibrosis induce a proinflammatory state in lung fibroblasts in vitro

Pulmonary matrix-derived hydrogels from patients with idiopathic pulmonary fibrosis induce a proinflammatory state in lung fibroblasts in vitro

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